A Transformative Decade: An Evaluation of the Francophone African Group of Pediatric Oncology's Training Program (2014-2024).

Childhood cancer in Africa faces significant challenges due to workforce shortages and limited training opportunities. The French African Group for Pediatric Oncology (GFAOP) established the African School of Pediatric Oncology and introduced a pediatric oncology teaching called the "Diplome Universitaire de Cancérologie Pédiatrique" (DUCP) training program. This report evaluates the contributions of the DUCP program to pediatric oncology in Africa and discusses the sustainability of the program. The DUCP program trained six cohorts of healthcare professionals from French-speaking African countries since 2014. An evaluation was done on the participant demographics and regional contributions. Data were collected from trainee records and DUCP records. The DUCP program was evaluated based on the domains developed by the Education Program Assessment Tool (EPAT). Over the 10-year period, the DUCP program trained 107 healthcare professionals from 20 Francophone countries of which 99% were retained in Africa. Of the 83 graduates, 55 (66%) actively practice in pediatric oncology. Of the 18 francophone countries, 17 countries increased the number of pediatric oncologists and 16 improved the ratio of pediatric oncologists to children under 15 years. Nine new pediatric oncology services were established by the graduates thus far. Despite challenges, such as the COVID-19 pandemic, the program remains sustainable because of continued financial support, collaborations with the international pediatric oncology community, and adapting the program content to participant and local setting needs. Retention of graduates in childhood cancer services remains a challenge that necessitates governmental involvement. The DUCP program is impactful and sustainable and improves access for children to cancer services in Africa. By fostering continued collaboration with governments, addressing the needs of an increasing African population, and expanding support for similar initiatives, the program's longevity and positive impact can be further ensured.

Genetic Diagnosis of Inborn Errors of Immunity in an Emerging Country: a Retrospective Study of 216 Moroccan Patients.

PURPOSE: Genetic testing provides great support to validate the clinical diagnosis of inborn errors of immunity (IEI). However, the high cost and advanced technology make these tests inaccessible to a large proportion of patients in low-income countries. In the present study, we aim to evaluate the Moroccan experience in genetic testing and to report the main molecular features and difficulties encountered in genetic diagnosis. METHODS: We performed a multi-center retrospective analysis of all patients with a molecular diagnosis and registered in the national registry between 2010 and 2022. To estimate the impact of the newly identified mutations, we calculated the Combined Annotation Dependent Depletion (CADD) score and the mutation significance cutoff (MSC) for each variant. RESULTS: A total of 216 (29%) patients received a genetic diagnosis out of 742 patients with IEI included in the registry. All genetic tests were performed in the context of thesis projects (40%) or international collaborations (60%). A set of 55 genetic defects were identified, including 7 newly reported: SNORA31, TBX21, SPPL2A, TYK2, RLTPR, ZNF341, and STAT2 GOF. Genetic diagnoses were more frequent in the defects of innate and intrinsic immunity with a percentage of 78%, while antibody deficiencies had a lower frequency with a percentage of 17.5%. Only one genetic diagnosis has been made in the complement deficiency group. The most commonly used molecular techniques were Sanger sequencing (37%) followed by targeted gene sequencing (31%). CONCLUSION: The thesis projects and collaborations were beneficial as they allowed us to provide a definitive genetic diagnosis to 29% of the patients and to contribute to the identification of new genetic defects and mutations. These results offer insight into the progress made in genetic diagnoses of IEI in Morocco, which would provide a baseline for improving the clinical management of patients with IEI.

Implementing the WHO Global Initiative for Childhood Cancer in Morocco: Survival study for the six indexed childhood cancers.

BACKGROUND: In 2018, the World Health Organization (WHO) launched the Global Initiative for Childhood Cancer (GICC). The goal is to achieve a global survival rate of at least 60% for all children with cancer by 2030. Morocco was designated as a pilot country for this initiative. PROCEDURE: This retrospective study included a cohort of children aged 0-15 years, with one of the six indexed cancers (acute lymphoblastic leukemia [ALL], Burkitt lymphoma [BL], Hodgkin lymphoma, retinoblastoma [RB], Wilms tumor or nephroblastoma, low-grade glioma), diagnosed between January 1, 2017 and December 31, 2019 at the six Moroccan Pediatric Hematology and Oncology units. Patients were followed-up until August 31, 2020. The Kaplan-Meier method was used to estimate survival rates, the log-rank test for comparing survival curves, and the Cox model for identifying prognostic factors. RESULTS: Data on 878 patients were included in the study. The most frequently reported cancer type was ALL (n = 383, 43.6%), followed by Wilms tumor (n = 139, 15.8%) and BL (n = 133, 15%). Most patients were less than 5 years of age (n = 446, 50.9%) and the male/female ratio was 1.46. The 1, 2, and 3-year overall survival rates were 80.1%, 73.6%, and 68.2%, respectively. In a multivariable Cox regression model, care center, cancer type, age group, and distance to the care center were statistically significantly associated to survival. Patients aged 10 years and older and patients living more than 100 km from the care center were more likely to die (respectively, HR = 1.39, p = .045 and HR = 1.44, p = .010). CONCLUSION: The reported results represent the baseline for measuring the impact of GICC implementation in Morocco.

Metro-SMHOP 01: Metronomics combination with cyclophosphamide-etoposide and valproic acid for refractory and relapsing pediatric malignancies.

BACKGROUND: In low- and middle-income countries, therapeutic options for advanced, refractory, or relapsing malignancies are limited due to local constraints such as cost of drugs, distance from oncology centers, and lack of availability of new anticancer drugs. Metronomics, which combines metronomic chemotherapy (MC) and drug repositioning, allows for the provision of new therapeutic options for patients in this setting. AIM OF THE STUDY: To evaluate the activity and toxicity of a metronomic regimen in Moroccan pediatric patients with refractory or relapsing malignancies. PATIENTS AND METHODS: From July 2014 to January 2018, patients with refractory/relapsing solid tumors treated in five pediatric oncology centers were consecutively enrolled. The metronomic regimen consisted of 28-day cycles with daily oral administration of cyclophosphamide (30 mg/m2 ) from days 1 to 21, together with oral etoposide (25 mg/m2 ) from days 1 to 21 followed by break of one week and daily valproic acid (20 mg/kg) from days 1 to 28. RESULTS: Ninety-eight children (median age, 8 years) were included. Underlying malignancies were neuroblastoma (24 patients), Ewing sarcoma (18), osteosarcoma (14), rhabdomyosarcoma (14), and miscellaneous tumors (28). A total of 557 cycles were given (median: 6; range, 1-18 cycles). One-year progression-free survival of our patients was 19%, and one-year overall survival was 22%. Complete response was obtained in three cases (3%), partial response in 11 cases (11%), and tumor stabilization for more than six months in 28 cases (28%). CONCLUSION: This three-drug metronomic combination was well tolerated and associated with tumor response and disease stabilization in 42 patients even for a long period.

Time to diagnosis of pediatric brain tumors: a report from the Pediatric Hematology and Oncology Center in Rabat, Morocco.

OBJECTIVE: Delayed diagnosis of pediatric brain tumors is known to occur worldwide but is not well studied in developing countries. Here, we examined the extent of delayed pediatric brain tumor diagnoses in Rabat, Morocco, and consider its potential causes and possible solutions. METHODS: We conducted a survey and interviews of the parents of children who were admitted to the Department of Hematology and Pediatric Oncology of Rabat Children's Hospital from January 1, 2016 to June 30, 2016. RESULTS: The families of 27 patients (14 girls and 13 boys) participated in the survey and interview. The median patient age was 7 years (range, 1-15 years). The most common presenting symptoms were vomiting (n = 18) and headache (n = 17). The tumor locations were supratentorial in 13 cases and infratentorial in 14 cases. The median time to diagnosis was 2 months (range, 0.25-20 months). The longest times to diagnosis occurred in children older than 5 years and in patients with supratentorial tumors or low-grade glioma. We did not observe any differences in the time to diagnosis according to sex, socioeconomic status, or urban or rural origin. CONCLUSIONS: Delayed diagnosis of pediatric brain tumors is a universal problem, evidenced by many studies in different countries. We propose that a paradigm shift in medical curricula addressing the delayed diagnosis of pediatric brain tumors should occur in medical schools and clinical training programs.

Improving the prognosis of pediatric Hodgkin lymphoma in developing countries: a Moroccan Society of Pediatric Hematology and Oncology study.

BACKGROUND: The event-free survival (EFS) of children with Hodgkin lymphoma (HL) exceeds 80% in high income countries (HIC), but little is known about this rate in developing countries. PROCEDURE: A prospective national protocol for children with classical HL was implemented in Morocco to increase EFS by careful risk stratification, providing each cycle of therapy on time, decreasing treatment abandonment, improving communication among healthcare providers, and improving data collection. Patients were stratified into a favorable risk group (Ann Arbor stages I and II, no B symptoms, no bulky disease, and no contiguous (E) lesions) and received four cycles of vinblastine, doxorubicin, methotrexate, and prednisone (VAMP) or an unfavorable risk group (all others) who received two cycles of vincristine, procarbazine, prednisone, and doxorubicin (OPPA) and four cycles of cyclophosphamide, vincristine, procarbazine, and prednisone (COPP). All patients received involved-field radiotherapy 25.5 Gy after completion of chemotherapy. EFS was calculated counting death, relapse/resistant disease, and abandonment as events. RESULTS: From February 2004 to December 2007, 160 patients enrolled; 138 (86%) had unfavorable risk features. Twenty patients (12.5%) abandoned treatment, 16 relapsed or had resistant disease, and 6 died (3 unexplained, 2 varicella, and 1 suicide). The estimated 5-year EFS was 70 ± 4% and overall survival 88 ± 3%. CONCLUSIONS: Good outcomes for pediatric HL patients can be achieved in LMIC using a multidisciplinary team approach, uniform protocol-based therapy, twinning partnership among oncology units in-country and abroad, and a data collection system to monitor compliance and identify gaps in care.

Saphenous Nerve Schwannoma: A Rare Differential Diagnosis of Knee Pain in Children.

Schwannomas are uncommon benign tumors of the peripheral nerves with a low risk of malignant transformation. They rarely affect children, can affect any part of the body but rarely occur in the lower extremity and typically present with a palpable mass, pain or neurological signs. Imaging helps to orient the diagnosis and anatomopathological examination helps to confirm it. We report a case of a 12-year-old girl who presented with left knee pain with subcutaneous mass overlying the tibial tuberosity medially. Clinical examination revealed a positive Tinel's sign. Magnetic resonance imaging (MRI) of the knee was performed, which revealed an encapsulated subcutaneous soft tissue mass overlying the tibial tuberosity medially, eccentric to the course of the infrapatellar branch of the saphenous nerve. The patient was operated with total intracapsular excision of the lesion and the anatomopathological study of the surgical specimen came back in favor of a schwannoma. Postoperatively, the patient showed a good recovery with disappearance of pain and swelling.

A rare presentation of a spinal diffuse midline glioma in a child: a case report.

Our patient had an extremely rare type of pediatric Diffuse Midline Glioma (DMG) with modified H3 K27 that occurred in the cervical spinal cord. Due to its location in the spinal cord, slow clinical presentation with torticollis for 7 months, and the non-specific radiological appearance of this tumour, it was initially considered to be a low-grade glioma. Based on imaging findings, the neurosurgery team performed a complete surgical resection, but the pathological features were consistent with a high-grade, diffuse midline glioma. Therefore, we are reporting a case of an altered high-grade DMG H3K27 glioma, which is difficult to diagnose due to its slow clinical symptoms which caused a delay in diagnosis, non-specific imaging, and with difficulty in accessing histopathological markers in low and middle income countries (LMIC).

The prevalence of anti-factor VIII and anti-factor IX antibodies among patients with hemophilia in Rabat, Morocco: a single center experience.

The emergence of anti-factor VIII and anti-factor IX antibodies in hemophilia A or B is the most serious complication of hemophilia. We aim to expose through a series of patient's data, collected between 02/2009 and 02/2016 in the pediatric service of university hospital of Rabat, Morocco, the epidemiological and clinical characteristics of these patients, and to highlight the therapeutic difficulties encountered during their treatment. Out of 120 hemophiliac patients, we included 22 hemophiliac patients (18.33%, p<0.004) who developed an antibody, 21 patients with hemophilia A. Among the patients, 54.5% (n=12) exhibited moderate hemophilia, while 45.5% (n=10) had major hemophilia. The average age at diagnosis is estimated to 12±6.6 years. The circumstances of diagnosis were dominated by therapeutic inefficiency (63.64% (n=14)), then came dental extraction (9.09% (n=2)), preoperative assessment 22.73% (n=5) and hemophiliac arthropathy in a single case. The titration of antibodies in a 12-person sample ranged from 0.6 UB to 84 UB, of which (41.67% (n=5)) were low responders. The therapeutic treatment was based on fresh frozen plasma (54.55% (n=7)), recombinant activated factor VII (18.2% (n=4)), recombinant activated factor VII and PFC (18.2% (n=4)), and induction of immune tolerance. The occurrence of an inhibitory antibody represents the major residual complication of replacement therapy.

Pediatric rhabdomyosarcoma in Morocco.

BACKGROUND: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in the first two decades of life. There is, however, a paucity of reports on the pattern of its occurrence in Africa. This study analyses the epidemiological pattern, clinical features, histology, and outcome in Moroccan children presenting with RMS. METHODS: We retrospectively studied 100 consecutive cases of histologically proven RMS in previously untreated children <15 years old followed at the Pediatric Oncology Unit of the Children's Hospital of Rabat from January 1995 to December 2004. RESULTS: RMS represented 5% of all the patients treated for cancer during this period. The male/female ratio was 2:1 with a mean age at diagnosis of 5 years. The embryonal subtype was the most frequent (73%) and the head and neck was the most common site of disease, followed by the genito-urinary tract and limbs. Chemotherapy was used in all patients; 44% also had a radical surgery and 23% radiation therapy. The event-free survival (EFS) at 10 years was 39% with relapse as the first cause of treatment failure. The overall survival at 10 years was 70%. The rate of treatment abandonment was 37%. CONCLUSION: Epidemiology and clinical features of RMS in Moroccan children does not differ from others countries. However, EFS is lower than that reported elsewhere due to occasional lack of availability of drugs, inadequate local control, and abandonment.

African School of Pediatric Oncology Initiative: Implementation of a Pediatric Oncology Diploma Program to Address Critical Workforce Shortages in French-Speaking Africa.

PURPOSE: In 2012, the French African Pediatric Oncology Group established the African School of Pediatric Oncology (EAOP), a training program supported by the Sanofi Espoir Foundation's My Child Matters program. As part of the EAOP, the pediatric oncology training diploma is a 1-year intensive training program. We present this training and certification program as a model for subspecialty training for low- and middle-income countries. METHODS: A 14-member committee of multidisciplinary experts finalized a curriculum patterned on the French model Diplôme Inter-Universitaire d'Oncologie Pédiatrique. The program trained per year 15 to 25 physician participants committed to returning to their home country to work at their parent institutions. Training included didactic lectures, both in person and online; an onsite practicum; and a research project. Evaluation included participant evaluation and feedback on the effectiveness and quality of training. RESULTS: The first cohort began in October 2014, and by January 2019, 72 participants from three cohorts had been trained. Of the first 72 trainees from 19 French-speaking African countries, 55 (76%) graduated and returned to their countries of origin. Four new pediatric oncology units have been established in Niger, Benin, Central African Republic, and Gabon by the graduates. Sixty-six participants registered on the e-learning platform and continue their education through the EAOP Web site. CONCLUSION: This training model rapidly increased the pool of qualified pediatric oncology professionals in French-speaking countries of Africa. It is feasible and scalable but requires sustained funding and ongoing mentoring of graduates to maximize its impact.

Macrophage activation syndrome associated with griscelli syndrome type 2: case report and review of literature.

Macrophage activation syndrome (MAS) is a severe and potentially fatal life-threatening condition associated with excessive activation and expansion of T cells with macrophages and a high expression of cytokines, resulting in an uncontrolled inflammatory response, with high levels of macrophage colony-stimulating factor and causing multiorgan damage. This syndrome is classified into primary (genetic/familial) or secondary forms to several etiologies, such as infections, neoplasias mainly hemopathies or autoimmune diseases. It is characterised clinically by unremitting high fever, pancytopaenia, hepatosplenomegaly, hepatic dysfunction, encephalopathy, coagulation abnormalities and sharply increased levels of ferritin. The pathognomonic feature of the syndrome is seen on bone marrow examination, which frequently, though not always, reveals numerous morphologically benign macrophages exhibiting haemophagocytic activity. Because MAS can follow a rapidly fatal course, prompt recognition of its clinical and laboratory features and immediate therapeutic intervention are essential. However, it is difficult to distinguish underlying disease flare, infectious complications or medication side effects from MAS. Although, the pathogenesis of MAS is unclear, the hallmark of the syndrome is an uncontrolled activation and proliferation of T lymphocytes and macrophages, leading to massive hypersecretion of pro-inflammatory cytokines. Mutations in cytolytic pathway genes are increasingly being recognised in children who develop MAS in his secondary form. We present here a case of Macrophage activation syndrome associated with Griscelli syndrome type 2 in a 3-years-old boy who had been referred due to severe sepsis with non-remitting high fever, generalized lymphoadenopathy and hepato-splenomegaly. Laboratory data revealed pancytopenia with high concentrations of triglycerides, ferritin and lactic dehydrogenase while the bone marrow revealed numerous morphologically benign macrophages with haemophagocytic activity that comforting the diagnosis of a SAM according to Ravelli and HLH-2004 criteria. Griscelli syndrome (GS) was evoked on; consanguineous family, recurrent infection, very light silvery-gray color of the hair and eyebrows, Light microscopy examination of the hair showed large, irregular clumps of pigments characteristic of GS. The molecular biology showed mutation in RAB27A gene confirming the diagnosis of a Griscelli syndrome type 2. The first-line therapy was based on the parenteral administration of high doses of corticosteroids, associated with immunosuppressive drugs, cyclosporine A and etoposide waiting for bone marrow transplantation (BMT).

Cytogenetic Profile of Moroccan Pediatric Acute Lymphoblastic Leukemia: Analysis of 155 Cases With a Review of the Literature.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common malignancy in children, with a peak incidence at 2 to 3 years of age and accounting for almost 30% of all cancers in this age group. It is well established that the identification of cytogenetic abnormalities is highly relevant for the prognosis of and therapeutic decisions in ALL. The purpose of the present study was to define the frequency of recurrent chromosomal abnormalities of ALL in Moroccan patients referred exclusively to the BIOLAB Laboratory of the Children's Hospital of Rabat during a 4-year period and compare our findings to the reported data. PATIENTS AND METHODS: We performed conventional karyotyping of 155 ALL cases, with a successful cell culture rate of 94%. RESULTS: We identified chromosomal abnormalities in 66% of the total studied cases, of which 70% revealed important recurrent abnormalities with high prognostic value, such as hyperdiploidy, hypodiploidy, t(9;22), t(8;14), t(1;19), and MLL rearrangements. In total agreement with the reported data, most of the patients (56%) in the present study were aged 1 to 5 years, with a male predominance, and B-ALL was the most common blast phenotype (85%). CONCLUSION: The frequency of most chromosomal rearrangements successfully identified in our study and their lineage correlated with those reported in the published data.

Primary atypical teratoid/rhabdoid tumor of the optic nerve: a rare entity in an exceptional location.

Atypical teratoid/rhabdoid tumors are rare and highly malignant central nervous system tumors. They have no specific radiological features and often present several histological components that make a problem in differential diagnosis with medulloblastoma and primitive neuroectodermal tumors. We present the case of a newborn girl complained of a gradual proptosis of the left eye secondary to an expansive lesional process of the optic nerve. The location at the optic nerve, reported only twice in the literature, and an exclusive rhabdoid appearance on biopsy added additional differential diagnosis problems. The proptosis worsened and the infant died few days after two cycles of chemotherapy. VIRTUAL SLIDES: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2037718783145212 .

[A hemophagocytic syndrome revealing a Griscelli syndrome type 2]. / Un syndrome d'activation macrophagique révélant un syndrome de Griscelli de type 2.

Griscelli syndrome type 2 is a rare autosomal recessive disorder, due to a mutation in RAB27A gene. It associates partial albinism, silver hair and immune deficiency. We report the case of a 6 year-old boy who was admitted to the Emergency department with severe sepsis complicated by hemophagocytic syndrome. Many clinical and biological criteria leads to the diagnosis of type 2 Griscelli syndrome: consanguineous family, recurrent infection, absence of psychomotor retardation, oculocutaneous albinism, silver hair, occurrence of hemophagocytic syndrome and especially the pathognomonic appearance on microscopic examination of the hair. The absence of giant organelles inclusion in all granulated cells eliminated Chediak-Higashi syndrome.